Calibration of ionization chamber for 18F and 68Ga

Carlos J. da Silva n, Estela M. de Oliveira, A. Iwahara, José U. Delgado,R. Poledna, Antônio E. de Oliveira, Denise S. Moreira, Ronaldo L. da Silva,Regio dos Santos Gomes, Eduardo V. de VerasLaboratório Nacional de Metrologia das Radiações Ionizantes (LNMRI), Instituto de Radioproteção e Dosimetria (IRD),Comissão Nacional de Energia Nuclear (CNEN), Av. Salvador Allende, s/no-Barra da Tijuca, CEP 22783-127, Rio de Janeiro, Brazil

H I G H L I G H T S

� Calibration figures were determined for 18F and 68Ge/68Ga.� The main components of uncertainty were determined.� Use long-lived 68Ge/68Ga as replacement for 18F in quality control of calibrators.� Sent four 68Ge/68Ga reference solutions to manufacturers of radionuclide calibrators.� A standardized 68Ge/68Ga solution was submitted to the SIR at BIPM.

a r t i c l e i n f o

Available online 11 December 2013

Keywords:StandardizationAnti-coincidence countingExtending dead time

a b s t r a c t

In order to maintain the results of primary activity standardizations carried out in 2011 the LNMRI hasdetermined the calibration factors for a pressurized 4π-ionization chamber for the nuclides 18F and 68Ga.This ionization chamber is coupled to a 6517A Keithley electrometer which is controlled by a homemadeLabVIEW program. This paper will describe the main issues related to the calibration of an ionizationchamber system for positron emitters and short half-life radionuclides such as timing, currentmeasurement, background, decay, and 226Ra check source measurements.

& 2014 Elsevier Ltd. All rights reserved.

1. Introduction

The cyclotron-produced radionuclide 18F is the most widelyused radiopharmaceutical for PET imaging with the chemical formof fluorodeoxyglucose (FDG) for diagnostic purposes (Schraderet al., 2007). The activity of the radiopharmaceutical administratedto patients is governed by regulations, and in the case of Brazil twofederal agencies are involved: the National Health SurveillanceAgency (ANVISA, Agência Nacional de Vigilância Sanitária, inPortuguese) and the National Commission on Nuclear Energy(CNEN, Comissão Nacional de Energia Nuclear, in Portuguese) forestablishing the quality control of such material. Since 1998, theNational Metrology Laboratory for Ionizing Radiation (LNMRI)has led a comparison program for activity measurements ofradiopharmaceutical administered to patients in Nuclear MedicineServices (NMS) with the purpose of promoting quality control. Theuse of Positron Emission Tomography (PET) as a tool for diagnosisof diseases, particularly cancer, continues to rise at a rate 20% per

year. Recently the LNMRI is including the Brazilian radiopharma-ceutical manufacturers in the comparison program.

Currently, there are four radiopharmaceuticals manufacturersin Brazil, all belonging to CNEN: IPEN in São Paulo city, IEN in Riode Janeiro city, CRCN in the Recife city and CDTN in Belo Horizontecity. The distance between IEN and LNMRI/IRD is about 20 km,however in the case of other manufacturers the distances aregreater than 500 km. In order to solve this problem the firstproposal is to work with a mock source of 68Ge/68Ga in order toimprove quality control of radionuclide calibrators for 18F nuclearmedicine services and manufacturers. For quality assurance ofthese measurements we sent a NIST ampoule with 68Ge to the SIR/BIPM program for establishing international traceability.

This work has been realized to determine the calibrationfactors for the LNMRI reference system based on a well typeionization chamber for 18F and 68Ga in order to guarantee trace-ability of these radionuclides at the national level. The proceedingsfor this determination are very simple and were made by deter-mination of relationship between current and activity for eachradionuclide in a standard geometry (source holder, ampoule typeand mass for each ampoule). The main difficulty for establishingthis calibration came from the primary standardization.

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Applied Radiation and Isotopes

0969-8043/$ - see front matter & 2014 Elsevier Ltd. All rights reserved.http://dx.doi.org/10.1016/j.apradiso.2013.11.137

n Corresponding author. Tel./fax: þ55 21 2173 2874.E-mail address: Carlos@ird.gov.br (C.J. da Silva).

Applied Radiation and Isotopes 87 (2014) 188–191

2. The 4π(α,β)-LS(γ) anti-coincidence measurement system

The LNMRI 4π(α,β)-LS(γ) anti-coincidence counting system hastwo photo-multipliers coupled to a 3″�3″ NaI(Tl) detector incorpo-rated in the gamma channel. The counting cell is made of poly-ethylene painted inside with TiO3 in order to reflect light. Live-timemeasurements with an extending dead time device in the anti-coincidence system were used to eliminate dead-time corrections(Baerg et al., 1976; Bouchard, 2000; Da Silva et al., 2012).

Since 2006 the LNMRI has performed the standardization of thefollowing radionuclides: 18F, 51Cr, 60Co, 67Ga, 68Ge/68Ga, 99Tc, 111In,123I, 124Sb, 131I, 166mHo, 177Lu, 241Am and 243Am. Within this system ofwork, the LNMRI has taken part in CCRI/BIPM international compar-isons for 99Tc, 124Sb and 177Lu with good performance.

The measurements in the anti-coincidence system have beenmade using a liquid scintillation counting in the beta channel anda NaI(Tl) scintillation detector in the gamma channel. Dead-timehandling in both beta and gamma channels (extendable deadtimes with live-time information) was employed via the use ofMTR2 modules developed at the LNHB (Bouchard, 2000) andallowed operation with dead time values from 25 to 200 μs. Thelive-time clock employed operated at a frequency of 1 MHz anddetails of the block diagram and counting cell can be found in DaSilva et al. (2008).

In the measurements of 18F and 68Ge in radioactive equilibriuma minimum dead time of 50 μs was employed to ensure adequatehandling of after-pulses from the photomultipliers.

3. Source preparation

From both master solutions of 18F and 68Ga an LNMRI ampoulecontaining 2.6 g and a NIST ampoule containing 3.5 g were pre-pared for measurement in the ionization chamber and germaniumspectrometer systems.

For the anti-coincidence counting, accurately weighed aliquotsfrom the radioactive solution were deposited into a commercialvial with 15 mL of Hisafe3 and Utima Gold without carrier for 18F.For this radionuclide six sources were prepared for each primarystandardization run, and four standardizations have been per-formed in this work.

In the case of 68Ga, nine sources were prepared in three typesof commercial scintillation cocktails: Hisafe3, Ultima Gold andInstagel plus, and for each cocktail type, 3 sources were prepared.

4. Standardization of 18F and 68Ge

For standardization of 18F by the live-timed anti-coincidencetechnique, the variation of efficiency from 0.97 to 0.75 was madeby electronic discrimination. The NaI(Tl) spectrum was gated on511 keV region using a single channel analyzer, and in this conditionthe main γ-ray counts were due to positon-annihilation decay. Fig. 1illustrates an efficiency extrapolation curve for 18F.

In the standardization of 68Ge, the LS positron efficiency, εβ wasvaried between 0.97 and 0.85 using electronic discrimination andextrapolated to unity in the usual manner. In order to avoid thecontribution of electron capture events from 68Ga, we cut theextrapolation curve in the region of low energy (adjusted to20 keV). The NaI(Tl) was gated on the 511 keV region using asingle channel analyzer, and as before, in this condition the mainγ-ray count rate contribution was due to positon-annihilationdecay. However, a contribution from the Compton scattering of1077 keV γ-rays (corresponding to electron capture events) ispresent, and therefore a correction to the intercept was necessary.In order to determine this correction, a 60Co source for this factor

was used in a similar manner to that proposed by Zimmermanet al. (2008). Fig. 2 presents one extrapolation curve obtained forHisafe cocktail.

Although LNMRI have also performed a standardization bysum-peak counting (De Oliveira, 2012) the LNMRI referencesystem with ionization chamber was calibrated for the activityvalue obtained by anti-coincidence system.

5. Measurement of impurities

No impurities above the detection limits of our Ge detectorspectrometer for 18F and 68Ga solutions were found.

6. Determination of calibration figures

In order to maintain the result of primary activity standardiza-tions made in 2011 the LNMRI has determined the calibrationfigure in a pressurized 4π-ionization chamber for 18F and 68Ga. TheLNMRI reference system works with a well-type Ionization cham-ber Centronic model IG11 with a filling gas of argon at a pressureof 2 MPa and it is coupled to a 6517A Keithley electrometer whichis controlled by a homemade LabVIEW program.

2640000

2660000

2680000

2700000

2720000

2740000

2760000

2780000

2800000

0 0.1 0.2 0.3 0.4 0.5 0.6

NN

/ NC

(Bq.

g-1)

(1- )/

18F Hisafe

Fig. 1. Extrapolation function obtained in the calibration of 18F.

240000

245000

250000

255000

260000

265000

270000

275000

280000

285000

290000

0.00 0.05 0.10 0.15

Ns-1

1-

68Ge Hisafe

Fig. 2. Extrapolation function obtained in the calibration of 68Ge.

C.J. da Silva et al. / Applied Radiation and Isotopes 87 (2014) 188–191 189

For the determination of calibration figure we adopt Eq. (1) thatis similar of proposal by Schrader et al. (2007);

F ¼ IPCGeom

AmIRaRTIRaRX

ð1Þ

where A is the activity per unit mass of the standard solution, m isthe ampoule mass, Ip is the current produced by standard solution,CGeom is the geometry correction factor (which in the standardmeasuring geometry is unity), and IRaRT/IRaRx is the relationbetween 226Ra currents check source at the time when the systembegin to operate at the time of calibration figure determination. Inall determination the correction for decay and backgroundwere made.

7. Results and discussion

Figs. 1 and 2 present the efficiency extrapolation curvesobtained by electronic discrimination for 18F and 68Ge. The activityreference value for 18F was 2.733 MBq/g and reference time is 12/15/2010 10:00. The activity reference value for 68Ge was321.217 kBq/g in 01/01/2011 12:00 UTC, in equilibrium conditionthe activity of 68Ge is equal the activity of 68Ga. In Tables 1 and 2we present the uncertainties of these primary standardizations.In the case of 18F, the timing is critical because of its short half-life.In Tables 3 and 4 we present the activities used in the determina-tion of calibration figures. Tables 5 and 6 present the calibrationfigures themselves, and in the case of the IG11 Centronic chamber

and LNMRI holder configuration, the calibration figures for 18F and68Ga differ depending on the type of glass ampoule employed. For68Ga the calibration factors were determined only for the activityof the daughter 68Ga, and the results are presented in Table 6 anduncertainty components are given in Table 7.

The combined standard uncertainty for the calibration figuresin both cases is lower than 1.0% and are more than adequatefor the nuclear medicine quality control requirements. Table 8

Table 118F uncertainty components for k¼1 (% of activity per mass).

Component due to Type 18F

Live time B 0.01Background B 0.04Mass B 0.05Extrapolation A 0.10Decay branch B 0.20Counting statistics A 0.20Half-life B o0.08Combined uncertaintya 0.31

a Components added in quadrature.

Table 268Ge/Ga uncertainty components for k¼1 (% of activity per mass).

Component due to Type 68Ge

Live time B 0.01Background B 0.04Mass B 0.05Extrapolation A 0.05Decay branch B 0.13Correction due to detection of 1077 keV photons B 0.10Counting statistics A 0.02Half-life B o0.01Combined uncertaintya 0.18

a Components added in quadrature.

Table 318F typical activity of ampoule solution.

Ampoule Activity (kBq) Mass Reference datea U (%) (k¼1)

LNMRI 168L10 10113.8 2.649218 10/11/2010 0.31LNMRI 169L10 31852.9 3.486974 10/11/2010 0.31

a Local time 12:00.

Table 468Ge/Ga typical activity of ampoule solution.

Ampoule Activity (kBq) Mass (g) Reference datea U (%) (k¼1)

LNMRI 03 873 2.7179 01/01/2011 0.18LNMRI 58L12 867 3.5346 17/01/2013 0.18

a Reference time: 12:00 UTC.

Table 518F results.

Ampoule type Calibrationfigure F (pA/MBq)

Standarduncertainty (%) (k¼1)

LNMRI ampoulea 40.8680 0.41NIST ampoulea 40.5842 0.41

a Standard measurement condition.

Table 668Ge/Ga results.

Ampoule type Calibrationfigure F (pA/MBq)

Standarduncertainty (%) (k¼1)

LNMRI ampoulea 40.14 0.22NIST ampoulea 39.78 0.28

a Standard measurement condition.

Table 7Uncertainty components for k¼1 (% of F).

Component due to Type 18F 68Ga

Timing B 0.05 0.05Background and current A 0.25 0.086Mass B 0.05 0.05uAs B 0.22 0.060uBs B 0.22 0.180Instability and 226Ra current A 0.06 0.04Half-life B 0.005 0.003Combined uncertaintya 0.41 0.22

uAs is addition in quadrature of uncertainties type A from anti-coincidencecounting.uBs is addition in quadrature of uncertainties type B from anti-coincidencecounting.

a Components added in quadrature.

Table 868Ge SIR/BIPM result.

Laboratory Ampoule Referencedate

Activity(kBq)

Equivalentactivity Ae

UAe

LNMRI/IRD

58L12 2012.04.03 867 15772 36 (k¼1)

C.J. da Silva et al. / Applied Radiation and Isotopes 87 (2014) 188–191190

presents the SIR/BIPM result for LNMRI 68Ge submission. TheLNMRI contribution for the SIR was the first submitted, andtherefore we must wait for another contribution in order to checkour performance. However, an international comparison exerciseis planned for 2014 under the auspices of the CCRI(II).

8. Summary

The use of the long lived 68Ge/68Ga radionuclide is proposed asan alternative means for nuclear medicine services to performquality control tests for 18F, especially for users situated at greatdistances from the national laboratories. The LNMRI has beenworking to implement this program with all Brazilian manufac-turers. Until now we do not have preliminary results in order toillustrate in this paper.

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